TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2113	6562;6563;6564	chr2:178775527;178775526;178775525	chr2:179640254;179640253;179640252
N2AB	2113	6562;6563;6564	chr2:178775527;178775526;178775525	chr2:179640254;179640253;179640252
N2A	2113	6562;6563;6564	chr2:178775527;178775526;178775525	chr2:179640254;179640253;179640252
N2B	2067	6424;6425;6426	chr2:178775527;178775526;178775525	chr2:179640254;179640253;179640252
Novex-1	2067	6424;6425;6426	chr2:178775527;178775526;178775525	chr2:179640254;179640253;179640252
Novex-2	2067	6424;6425;6426	chr2:178775527;178775526;178775525	chr2:179640254;179640253;179640252
Novex-3	2113	6562;6563;6564	chr2:178775527;178775526;178775525	chr2:179640254;179640253;179640252

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-10
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1822
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/E	rs1574647040	None	0.822	D	0.497	0.822	0.502379540653	gnomAD-4.0.0	1.59076E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8566E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.9275	likely_pathogenic	0.9352	pathogenic	-0.781	Destabilizing	0.86	D	0.534	neutral	None	None	None	None	N
K/C	0.8827	likely_pathogenic	0.9021	pathogenic	-0.978	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
K/D	0.992	likely_pathogenic	0.9924	pathogenic	-0.386	Destabilizing	0.915	D	0.605	neutral	None	None	None	None	N
K/E	0.8347	likely_pathogenic	0.8409	pathogenic	-0.269	Destabilizing	0.822	D	0.497	neutral	D	0.722158998	None	None	N
K/F	0.9654	likely_pathogenic	0.9672	pathogenic	-0.694	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	N
K/G	0.9719	likely_pathogenic	0.9731	pathogenic	-1.137	Destabilizing	0.754	D	0.619	neutral	None	None	None	None	N
K/H	0.5914	likely_pathogenic	0.6207	pathogenic	-1.608	Destabilizing	0.956	D	0.687	prob.neutral	None	None	None	None	N
K/I	0.7872	likely_pathogenic	0.8048	pathogenic	0.14	Stabilizing	0.971	D	0.807	deleterious	D	0.594661681	None	None	N
K/L	0.7724	likely_pathogenic	0.792	pathogenic	0.14	Stabilizing	0.956	D	0.658	neutral	None	None	None	None	N
K/M	0.7063	likely_pathogenic	0.7257	pathogenic	0.1	Stabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	N
K/N	0.9626	likely_pathogenic	0.9652	pathogenic	-0.684	Destabilizing	0.032	N	0.389	neutral	D	0.684972026	None	None	N
K/P	0.9981	likely_pathogenic	0.9983	pathogenic	-0.138	Destabilizing	0.978	D	0.655	neutral	None	None	None	None	N
K/Q	0.3333	likely_benign	0.3548	ambiguous	-0.792	Destabilizing	0.942	D	0.535	neutral	D	0.673786874	None	None	N
K/R	0.082	likely_benign	0.0815	benign	-0.695	Destabilizing	0.014	N	0.435	neutral	N	0.521760456	None	None	N
K/S	0.9496	likely_pathogenic	0.954	pathogenic	-1.387	Destabilizing	0.754	D	0.487	neutral	None	None	None	None	N
K/T	0.8447	likely_pathogenic	0.8586	pathogenic	-1.056	Destabilizing	0.822	D	0.597	neutral	D	0.722686933	None	None	N
K/V	0.7588	likely_pathogenic	0.78	pathogenic	-0.138	Destabilizing	0.978	D	0.705	prob.neutral	None	None	None	None	N
K/W	0.9228	likely_pathogenic	0.9227	pathogenic	-0.557	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
K/Y	0.9038	likely_pathogenic	0.9097	pathogenic	-0.205	Destabilizing	0.993	D	0.757	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.